Articles

This picture is by Darryl Leja, NHGRI. It is in the public domain at http://www.genome.gov

Should you and your family be tested for genetic conditions that can cause blood clots? After you have had a pulmonary embolism or DVT (deep vein thrombosis) you may think that the answer is an easy, “YES!” It isn’t. Genetic testing comes at a price. You need to know what that price is and if you are willing to pay it. You also need to know if you are willing to make that decision for your children and other family members. Get ready for a quick ride through genetics, genetic testing, and the dark side of testing for genetic blood clotting conditions.

Blood clotting conditions raise the risk of forming blood clots in the lungs (pulmonary embolism) or in the large veins in your body (deep vein thrombosis). These clots can be very serious and often have a lengthy recovery period. Sometimes these clots are fatal.
We can break clotting conditions into two general groups: genetic and non-genetic. Genetic clotting conditions come from one of your parents by way of the genes that were carried in an egg or sperm cell when you were conceived. Non-genetic clotting conditions do not come from your parents. These can come from things like cancer, other diseases, or things that we haven’t discovered yet. We are going to focus on the first group, clotting conditions that are caused by genetics.

When you were conceived you received genetic material from your mother and father. For instance, I have blue eyes. I have one gene for blue eyes from my mother and one gene for blue eyes from my father. I also have a clotting condition called Factor V Leiden. I have one good copy of the Factor V Leiden gene. It came from my mother. I also have one mutated gene from my father. (We will come back to this a little later.)

Your DNA looks a bit like a spring shaped ladder. It is made up of 4 chemicals that we typically refer to in an abbreviated form: A, G, T, and C. Each ladder rung has a pair of letter with one side from mom and the other side from dad. Each ladder rung is responsible for an instruction about who and what you are. Scientists have mapped out these ladder rungs. Each step is a location and each location has certain patterns of A, G, T, C that are acceptable. If just one of those letters is off, your genetic code has a “mutation”. Mutations may do something small like change your hair color. Unfortunately, mutations can also do something more serious like impacting how your blood clots. These blood clotting mutations are what doctors are looking for when they run tests for genetic blood clotting conditions.

Genetic testing takes some material from your body, pulls out the DNA, and then looks at certain sections of that DNA to see if it has the correct chemicals in the correct places. For example, one wrong letter in this section of DNA causes Factor V Leiden: GCAAGAACTGCAGGGGAGGAGGACGCTGCCACCCACAGCCTCTAGAGCTCATTGCAGCTGGGACAGCCCGGAGTGTGGTTATGTTTGGGCTATTATCTAATGCTGTGTAGAAATATTAAAACCCCTGTTATTTTGAAATAAAAAAGATACCCACTTTT. A DNA test scans for mistakes and uses them to identify any clotting conditions.

DNA testing has a number of benefits. First, these tests are very accurate because your DNA never changes. You get your DNA at conception and you have the same DNA throughout every cell in your body your entire life. Blood clots and anticoagulation will not change your DNA. Second, DNA tests may also help other family members understand any increased blood clots risks. As DNA is passed through parents to offspring you can figure out who should watch carefully for clots without having them tested. Lastly, DNA testing can be done before something goes wrong. Your doctor can test you and warn you of potential health issues before they happen. This gives you a chance to avoid problems that faulty DNA may cause.

So, if DNA testing is so useful, why am I writing an article about the dark side of genetic testing? Knowing your DNA comes at a cost. You may learn that you or your family member has an incurable condition. You may pay for a test that doesn’t matter because the disease never would have showed up in that person. (Factor V Leiden only has a 1 in 10 chance of causing a clot!). DNA testing may cause unneeded fear and stress. Low risk clotting conditions typically are not medicated as the medication is higher risk than the chance of serious illness from a clot. Someone may end up taking unneeded medication and have serious side effects. Medical treatment after genetic testing isn’t always clear.

Health isn’t the only risk with DNA testing. There is another very large and very real risk with genetic testing, discrimination. In 2008 the Genetic Discrimination Nondiscrimination Act (GINA) was enacted to protect Americans from job and medical insurance discrimination from results of genetic testing. GINA ensures that health insurance companies cannot ask you about any DNA testing or any DNA test results when you apply for insurance. GINA also states that employers may not ask for the results of DNA testing when making hiring or promotion decisions. GINA is a good start but there are still many places that can discriminate based on genetic test results.

Genetic discrimination can still be found in many places. Life insurance, annuities, banks, home insurance, travel insurance, and disability insurance can all review the results of past DNA testing before determining eligibility. It doesn’t matter when the testing occurred. A parent may have a 6-year-old child tested for genetic clotting conditions. When the child is 46 that genetic information may still disqualify him or her from participating in certain services. Your DNA never changes so the results of a DNA test will follow you forever, even if you were not the person that decided to have the test done. Another place discrimination shows up is in subconscious discrimination. A possible date might turn a woman down to blood clot risks in pregnancy. You may be passed over for a job after your workplace hears about your results because your boss is subconsciously concerned that stress may cause clots. Some of these forms of discrimination are obvious, some are not. They all share one thing in common: they are a result of a DNA test.
DNA testing is often used when blood clots occur. DNA testing can help you to determine your treatment. It can also help family members avoid future clots. The problem is that genetic testing, like all medical procedures, should be weighed carefully. Some people want to have all of their children and close family members tested. I recommend talking to different doctors before jumping into family blood testing. If the blood testing will have a significant impact in medical treatment it may be warranted. On the other hand, if the DNA test is being used as nothing more than a precaution, you may decide that your own clotting history is enough precaution on its own. Ask your doctor how treatment will change based on the DNA test results. The social and monetary costs must be determined and considered.

Back to my story...
After my clots in 2008 we decided not to have my parents tested. As a family we did inform other family members of my medical history and Factor V Leiden diagnosis so that they could be on the lookout for clots and could enact clot prevention strategies. Since then both of my parents had surgery. While the doctor didn’t require it, they chose to have Factor V Leiden testing. My dad was my gene donor. It didn’t change their surgeries much. My mom who does not have Factor V Leiden was given pressure cuffs and anticoagulation as she had a high risk surgery. My dad’s surgery was much less serious and had the pressure cuffs while in surgery. Thankfully, neither clotted.

For more information about genetic testing I highly recommend an episode of Neil DeGrasse Tyson’s podcast called Star Talk. Season 7, episode 9 is titled The Promise and Peril of the Genomic Revolution. It features one of the founders of 23 and Me and discusses the morality and future of genetic testing. This episode can be found here: https://soundcloud.com/startalk/the-promise-and-peril-of-the-genomic-revolution or you can listen to it below.

After a blood clot, tests can be run to determine if you have a condition that makes your blood clot more easily than the majority of the population. These conditions are often referred to as clotting conditions, thrombophilia, or hypercoagulable states. Testing for these conditions will not be able to predict who will and will not have a clot. About half of the people who have a clot will have no known cause. This means that the blood work would show no clotting conditions.

Testing for thrombophilia is useful when deciding the length of time a patient will be on anticoagulants. The problem with anticoagulants is that they are risky. You only want to be on anticoagulants if the risk of clotting is larger than the risk of a life threatening bleed. Testing for thrombophilia will give you more information so that you and your doctor can determine which risk is more acceptable for you.

To determine if thrombophilia testing is right for you, you should:

Ask your doctor if having thrombophilia would change his or her recommendations about the amount of time that you will take anticoagulant medications. If the test will not change treatment, the test is not needed.

Talk with your doctor and insurance agents about the impact the findings may have on your ability to obtain life insurance.

Consider your age. Many recommendations state that individuals under the age of 50 that had a DVT or PE without a significantly large risk factor (abdominal surgery, bed ridden, cancer, or other major risks) have tests run to see what may have caused the clot.

Consider your risks. Can you and your doctor identify any MAJOR risks? A major risk may be able to be eliminated so that the clot doesn't repeat. If you only had a minor risk (weight and birth control are examples) there is a good chance that something else contributed to your clot.

Ask your medical team what they feel are typical, minor, and major risks for blood clots and figure out where you fit into that list.

Consider what risks will be in your future. Are you thinking about birth control, infertility treatments, cancer, hormone replacement, frequent long haul airplane trips, or any other big risks? You may want to know if you have a clotting condition that will put you at further risk.

Is there a family history of clotting or miscarriage? If there is, let your doctors know!

Think about your history, the costs, risks, and benefits. Medical testing seems harmless but it can have unwanted effects. If you need help deciding about testing please talk to your primary care provider and consider requesting a hematology consult. Feel free to get a second opinion. Many times doctors will write off a clot as a simple case of birth control pills, weight, or travel when there might be more to the story. If you haven't experienced a recent major risk factor there is a good chance that there is more to your clot's story.

After having a pulmonary embolism or DVT survivors begin to wonder about testing for blood clotting conditions and thrombophilia. There are genetic tests and blood chemistry tests that can be done to evaluate the survivor's risk of clotting. If a genetic test comes back positive it is now time to decide if family members should also be screened for clotting conditions.

In my case I had some testing done immediately after I was diagnosed with pulmonary embolisms while I was still in the hospital. While the blood chemistry tests are useless while on warfarin and heparin the genetic tests came back with useful information. My hematologist found out that I have heterozygous Factor V Leiden.

Factor V Leiden is a mutation of one of the pieces of genetic information that tells the blood how to turn off clotting when it isn't needed. In my case it is heterozygous. This means that I have one good copy and one bad copy of the Factor V Leiden gene. The mutated versions of my turn off system don't match the chemical that is responsible for turning clotting off. I am lucky in that the other half of my turn off system is programed correctly. This gives me a much lower chance of having clots than if I had two mutated genes.

Being heterozygous also gives me a hint about why I have Factor V Leiden. One of my parents passed on the gene to me. This means that at least one of my parents has either homozygous or heterozygous Factor V Leiden.

When I was first diagnosed one of the first questions to my hematologist was, "should my family be tested?" My hematologist felt that my clotting condition wasn't a major risk so genetic testing wouldn't be warranted. He also noted that it would be helpful to let family members know that they may be at risk.

While informing my family about the risk we discovered that someone on my mom's side also has Factor V Leiden. This seemed to be the missing link. We assumed that my mother was the carrier that gave me my gene.

Fast forward a few years...

This last fall my dad had to go in for hernia repair surgery. Knowing my history he shared our family history of pulmonary embolisms and my Factor V Leiden diagnosis. Arrangements were made to test him for Factor V Leiden. We expected it to be negative due to history on my mom's side. The tests came back positive. He also has heterozygous Factor V Leiden. Arrangements were made to consult with a hematologist and make clotting plans for his surgery. His hematologist, the same one that I see, cleared him for surgery with no anticoagulants as he felt that laparoscopic hernia repair was a very low risk surgery.

Come May we discovered that my mom had a number of benign tumors that needed to be removed. Due to the history she also asked for a Factor V Leiden test. Her test came back negative. Despite that her surgeon has her on Lovenox injections. Abdominal surgery is a very high risk for clotting in ALL people. New standards for clot prevention are demanding that preventative anticoagulation be used after high risk surgeries. While in recovery her heart rate was up. As an additional precaution she was sent to have a chest CT to make sure that she didn't have clots. She was clear. We now need to make it through recovery with no clots. I am hoping that her lack of FVL diagnosis and the daily Lovenox injections keep her clot free.

If you would like more information about who should be tested for thrombophilia please see this Clot Connect article.

MTHFR is a genetic mutation that will sometimes increase the risk of blood clots. MTHFR is caused by a change in the methylenetetrahydrofolate reductase (NAD(P)H) gene. This gene is also known simply as MTHFR. MTHFR carries the instructions for making an enzyme called methylenetetrahydrofolate reductase. One of the most important things that this enzyme does is to convert an amino acid homocysteine into another amino acid, methionine. The body then uses the new amino acid to make a number of different proteins in the body.

HOW DOES MTHFR AFFECT CLOTTING?Some individuals who have the MTHFR gene mutation develop elevated levels of homocysteine. Elevated levels of homocysteine have been associated with an increased risk of blood clots. Individuals who have a MTHFR mutation and have normal levels of homocysteine are not at an increased risk of clotting. It is the elevated homocysteine that raises the risk of clots, not the MTHFR mutation.

HOW IS MTHFR DIAGNOSED?MTHFR is diagnosed by measuring the levels of homocysteine in the blood. MTHFR is not a large risk factor for blood clots. For this reason, some doctors will limit homocysteine testing to individuals who are under 30 years of age who have a blood clot or have a history of repeated blood clots.

TREATMENTThe best way to prevent clots is always to use good clotting hygiene. Make sure to keep moving, be careful on long car rides and flights, stay hydrated, and to speak with a doctor for extended illnesses or surgeries. If blood clots are a problem, anticoagulation therapy may be useful. Vitamins B12 and B6 are involved in lowering homocysteine levels in the body. Studies haven't clearly shown a decrease in blood clotting risk when patients take B6 and B12. If you have elevated homocysteine levels, it would be worth asking your doctor how he or she feels about using B vitamins to prevent clots.

Today, another study has been released that further supports the notion that migraine and blood clots are closely linked. Glynn (2012) shares that the study observed a total of 145,304 females who were using contraceptives. 2,691 participants were affected by migraine with aura and 4,437 were affected by migraine without aura. During the study, 7.5% of the women who suffered from migraine with aura who were using a newer generation combined oral contraceptive developed a deep vein thrombosis. Only 6.3% of the women in the migraine without aura group developed a deep vein thrombosis.More blood clot complications occurred in the migraine with aura group than in the migraine without aura group. For this reason, migraine with aura needs to be discussed with your doctor as a risk factor for blood clots. This is especially important for women using third generation contraceptives. (Yasmin, Ocella, and Yaz are examples of third generation combined oral contraceptives.)

This isn't the first study to link blood clots and migraine. Ferrara et al. (2012) found a relationship between migraine and elevated levels of Factor VIII and Factor IX. They also found that individuals with migraine were more likely to have either MTHFR or Factor V Leiden. In 2011, Kutal et al had almost identical results in a similar study. It seems safe to assume that there is a connection between migraine and thrombophilia.

Boyles (2008) points out, that we do not know for sure if thrombophilia is the link between migraines and blood clots. There could be another factor involved.

No matter what the link is between migraine and blood clots, patients need to make sure that doctors are aware of the blood clot risks associated with migraine, especially in those patients who have multiple blood clot risk factors.

This site generates income for webmaster based on affiliate relationships with our partners, including Amazon, Zazzle, VigLink, CafePress, Google, and others.

Medical information provided at your own risk. The webmaster is not a healthcare professional. Please work with your doctor regarding any medical concerns. Blood clots are a life threatening condition and must receive appropriate medical care.